Matuszewska B, Keogan M, Fisher D M, Soper K A, Hoe C M, Huber A C, Bondi J V
Department of Pharmaceutical Research and Development, Merck Research Laboratories, West Point, Pennsylvania 19486.
Pharm Res. 1994 Jan;11(1):65-71. doi: 10.1023/a:1018993610801.
The efficacy of topical formulations of acidic fibroblast growth factor (aFGF) in healing of full-thickness wounds has been studied in a diabetic db+/db+ mouse model. The effect of several formulation variables, dose, and application frequency was examined. It was found that wound healing in diabetic animals treated with aFGF or placebo was slower than in their nondiabetic littermates. The availability of aFGF from the viscous vehicle employed in this study (1% hydroxyethyl cellulose) was demonstrated in vitro using diffusion cells. The viscous formulation of aFGF was equally effective in wound healing as a nonviscous formulation in phosphate-buffered saline. A formulation containing heparin (necessary for full biological and conformational stability of aFGF) at a mass ratio of 3:1 to aFGF was more efficacious than formulations with lower heparin: aFGF ratios. Wounds treated with three doses of 3.0 micrograms/cm2 aFGF healed faster than those treated with a single dose of 3.0 micrograms/cm2 aFGF. Three applications of 3.0 or 0.6 microgram/cm2 a FGF were equally effective in accelerating wound healing.
在糖尿病db+/db+小鼠模型中研究了酸性成纤维细胞生长因子（aFGF）局部制剂对全层伤口愈合的疗效。研究了几个制剂变量、剂量和给药频率的影响。结果发现，用aFGF或安慰剂治疗的糖尿病动物的伤口愈合比其非糖尿病同窝动物慢。使用扩散池在体外证明了本研究中使用的粘性载体（1%羟乙基纤维素）中aFGF的可用性。aFGF的粘性制剂在伤口愈合方面与磷酸盐缓冲盐水中的非粘性制剂同样有效。与肝素：aFGF比例较低的制剂相比，含有肝素（aFGF完全生物学和构象稳定性所必需）且与aFGF质量比为3:1的制剂更有效。用三剂3.0微克/平方厘米aFGF治疗的伤口比用单剂3.0微克/平方厘米aFGF治疗的伤口愈合更快。三次应用3.0或0.6微克/平方厘米aFGF在加速伤口愈合方面同样有效。
